Moxifloxacin Micronization via Supercritical Antisolvent Precipitation

Supercritical antisolvent (SAS) precipitation is employed for micronization of moxifloxacin (MF), an antibiotic from the fluoroquinolone group, to develop new dosage forms of MF. With this technique, we produced, in a controllable fashion, MF particles with different sizes (0.6–8.0 μm) and morphologies (from polygonal sheets to elongated rectangular prisms). The infrared and circular dichroism spectroscopy data suggest that micronization of MF via SAS does not alter its chemical structure or cause racemization. We demonstrate that micronized forms of MF drug substance exhibit a 20 to 30% increase in the dissolution rate, as compared to the initial MF form, in a physiological medium (pH 7.4). The dissolution rate of the microparticles obtained via SAS micronization depends on their size, morphology, and degree of crystallinity. The various data obtained in this study will be used in formulating new dosage forms of MF for treatment of drug-resistant forms of tuberculoses.     

Polymorphism of Risperidone in Supercritical Fluid Processes of Micronization and Encapsulation into Aliphatic Polyesters

The specific features of the transformation of risperidone polymorphs as a result of micronization and encapsulation into aliphatic polyesters (polylactides and polylactoglycolide) have been studied using supercritical (SC) carbon dioxide. It has been shown that the micronization of risperidone, which originally is polymorph A, via the rapid expansion of supercritical solutions (RESS) and the supercritical antisolvent (SAS) precipitation leads to its crystallization in less thermodynamically stable polymorph B. This transition is complete for SAS and only partial for RESS. When these micronized samples are encapsulated into polylactides and polylactoglycolides via the formation of particles from gas-saturated solutions (PGSS) and monolithization with further cryogrinding (MCG), risperidone polymorph B is partially converted back into polymorph A. At the same time, the micronization of initial risperidone polymorph A via cryogrinding and its further PGSS and MCG encapsulation into polylactides or polylactoglycolides does not result in any change in the polymorphic state of risperidone, and it always remains in initial polymorph A.     

Supercritical fluid micronization of risperidone pharmaceutical substance

A comparative study of the supercritical fluid micronization of risperidone pharmaceutical substance with an initial particle size of 50 to 100 μm by the RESS and SAS methods aimed at increasing the bioavailability of risperidone as a drug was performed. Both methods makes it possible to prepare risperidone particle of various forms, 5–20 μm in size. However, the SAS method is preferable, because in contrast to RESS, it does not cause contamination of risperidone with organic solvents used in both processes or any other impurities and also makes it possible to vary the shape and size of particles. It is shown that, during SAS micronization, the polymorphic form of risperidone changes from triclinic to monoclinic.     

Preparation of nanoparticles of poorly water-soluble antioxidant curcumin by antisolvent precipitation methods

The objective of this study was to enhance the solubility and dissolution rate of a poorly water-soluble antioxidant, curcumin, by fabricating its nanoparticles with two methods: antisolvent precipitation with a syringe pump (APSP) and evaporative precipitation of nanosuspension (EPN). For APSP, process parameters like flow rate, stirring speed, solvent to antisolvent (SAS) ratio, and drug concentration were investigated to obtain the smallest particle size. For EPN, factors like drug concentration and the SAS ratio were examined. The effects of these process parameters on the supersaturation, nucleation, and growth rate were studied and optimized to obtain the smallest particle size of curcumin by both the methods. The average particle size of the original drug was about 10–12 μm and it was decreased to a mean diameter of 330 nm for the APSP method and to 150 nm for the EPN method. Overall, decreasing the drug concentration or increasing the flow rate, stirring rate, and antisolvent amount resulted in smaller particle sizes. Differential scanning calorimetry studies suggested lower crystallinity of curcumin particles fabricated. The solubility and dissolution rates of the prepared curcumin particles were significantly higher than those the original curcumin. The antioxidant activity, studied by the DPPH free radical-scavenging assay, was greater for the curcumin nanoparticles than the original curcumin. This study demonstrated that both the methods can successfully prepare curcumin into submicro to nanoparticles. However, drug particles prepared by EPN were smaller than those by APSP and hence, showed the slightly better solubility, dissolution rate, and antioxidant activity than the latter.     

SCF micronization of poly-3-hydroxybutyrate using supercritical antisolvent

Micronization of poly-3-hydroxybutyrate (PHB) by the supercritical fluid antisolvent precipitation (SAS) technique using supercritical carbon dioxide as an antisolvent was studied experimentally. The possibility of preparing particles of varying morphology (including hollow spheres) and specified size from 100 nm to 20 μm was demonstrated. The influence of different mechanisms of solid phase formation during SAS micronization on the size and morphology of PHB microparticles under different experimental conditions was considered.     

Preparation of hydroxypropylmethylcellulose microparticles using supercritical antisolvent precipitation

Micronization of hydroxypropylmethylcellulose using supercritical antisolvent (SAS) method is studied. The influence of various parameters, such as solvent type, polymer concentration, pressure, solution to supercritical CO₂ flow rate ratio on morphology of particles is discussed. The possibility of obtaining spherical or elliptical shape hydroxypropylmethylcellulose particles of submicron size (190–620 nm) that depends on the process parameters is demonstrated.     

Processes of dissolution and hydrate formation behind a shock wave in a liquid with carbon dioxide bubbles

The processes of dissolution and hydrate formation behind the front of a shock wave of moderate amplitude in water with carbon dioxide bubbles are studied experimentally at various initial static pressures. The influence of a surface-active substance (SAS) in the medium on the processes of dissolution and hydrate formation behind the shock wave is investigated. It is demonstrated that behind a shock wave of moderate amplitude in a liquid with carbon dioxide bubbles an intensive process of dissolution and hydrate formation takes place, resulting in complete disappearance of the gas phase in a matter of a few milliseconds. The presence of an SAS in the medium does not significantly influence the processes of dissolution and hydrate formation within the investigated periods of time.     

Target morphologies via a two-step dissolution-quench process in polymer blends

A novel process for obtaining controlled morphologies in polymer blends is modeled numerically. Particles of one type of polymer are allowed to dissolve in a matrix of a dissimilar polymer. Prior to complete dissolution the blend is quenched into the two-phase region, such that phase separation takes place. The combination of the incomplete dissolution and the wavelength selection process associated with phase separation results in particles that during the "intermediate" stages have a core that is significantly richer in the matrix material.     

Investigation of dissolution kinetics for high rates of dissolution

A procedure was developed for investigating the dissolution of crystals that rub against a substrate with the solvent, whereby the process becomes significantly intensified. A theory of the method is presented. The kinetics of dissolution of azobenzene in alcohol at different rates of substrate motion, normal loads on the crystal, and temperatures is investigated. It is shown that a diffusion-kinetic regime of dissolution is realized under these conditions. An estimate of the kinetic dissolution coefficient (K 1–15 cm/sec) yields a high value that does not agree with the concepts of the tangential mechanism, and indicates a normal mechanism of the process. The probable mechanism of crystallization of azobenzene from alcohol is tangential, and there is no quantitative reversibility of the crystallization and dissolution.Translated from Izvestiya Vysshikh Uchebnykh Zavedenii, Fizika, No. 12, pp. 18–24, December, 1970.     

Antioxidative properties of lactoferrin from bovine colostrum before and after its lyophilization

The effect of lactoferrin (LF) derived from native, frozen and lyophilized bovine colostrum on the intensity of free-radical processes in model systems has been investigated. It was shown that LF, not depending on the source of its obtaining, is an efficient iron chelator and decreases intensity of peroxidative processes. It was established, that antioxidative properties of LF from lyophilized colostrum have remained unchanged within 12 months of dry colostrum storage under proper conditions.     

Effect of solvent type and concentration on size and morphology of arbidol microparticles obtained by supercritical antisolvent precipitation

The capability of arbidol microparticle preparation by supercritical antisolvent (SAS) precipitation was demonstrated. A nonmonotonic dependence of the average particle size on the concentration was found, while the position of the minimum is dependent on the type of solvent used. It is possible to prepare Arbidol particles of various morphology and size from several microns to several hundred microns depending on the conditions.     

Unique Morphology in Polylactide/Graphene Oxide Nanocomposites

Polylactide (PLA)/graphene oxide (GO) nanocomposites with different GO loadings were prepared by solution blending using tetrahydrofuran (THF) as solvent. The morphologies of the nanocomposites in the cast films and in subsequently isothermally crystallized samples were investigated separately. According to polarized optical microscopy images of the composites after isothermal crystallization, it was deduced that GO had nucleation effects on the crystallization of PLA and led to the size of spherulites decreasing and the number of spherulites increasing. However, by virtue of SEM, unique microsphere morphologies were found in the cast films of the PLA/GO composites. It was found that the features of this kind of microsphere were not influenced by the compositions but by the evaporation rate of the solvent during the preparation of the cast films. A faster evaporation rate of solvent resulted in smaller size of the microspheres. Based on DSC and FTIR results, it was proposed that the forming of this kind of microsphere was related to hydrogen bonds being formed between PLA and GO. The unique microsphere morphology is suggested to provide a new method to prepare PLA microsphere-based scaffolds.     

微波辅助萃取水蒸气蒸馏技术在中药有效成分分析中的应用研究

采用微波辅助萃取-水蒸气蒸馏方法提取中药制剂的有效成分,结合紫外分光光度法测定其含量。以提取六味地黄丸中有效成分丹皮酚为试验对象,探讨了微波辅助萃取的实验条件,优化的实验条件是:以乙醇+水(V/V,1∶2)为萃取溶剂,样品与溶剂比1∶50(W/V),微波功率380W,辐射时间2min。结果表明采用微波辅助水蒸气蒸馏对中药制剂进行预处理,可以明显加快丹皮酚的溶出速率,缩短水蒸气蒸馏的时间,将方法应用于牡丹皮及4种中药制剂中丹皮酚的测定,结果满意。     

Effect of electric field on the percolation phase transition in lead scandotantalate single crystals

The effect of a dc electric field on the phase transition process in lead scandotantalate single crystals differing in the degree of ion ordering has been studied by small-angle light scattering (SAS). The spontaneous phase transition occurring in these crystals is shown to be accompanied by a sharp SAS intensity peak indicating the percolation nature of this transition. A phase diagram in the field-temperature coordinates has been constructed for all the PST crystals studied in the work. The electric field and the temperature variation rate have been found to affect the SAS intensity.     

Dissolution behaviour of the barrier layer of porous oxide films on aluminum formed in phosphoric acid studied by a re-anodizing technique

Chemical dissolution of the barrier layer of porous oxide films formed on aluminum foil (99.5% purity) in the 4% phosphoric acid after immersion in 2 mol dm⁻³ sulphuric acid at 50 °C has been studied. The barrier layer thickness before and after dissolution was determined using a re-anodizing technique. A digital voltmeter with a computer system was used to record the change in the anode potential with re-anodizing time. It has been found that the barrier layer material may consist of two or three regions according to the dissolution rate. The barrier oxide contains two layers at 35 V: the outer layer with the highest dissolution rate and the inner layer with low dissolution rate. The barrier oxide contains three layers at 40 V and above it: the outer layer with high dissolution rate, the middle layer with the highest dissolution rate and the inner layer with low dissolution rate. It has been shown that there is a dependence of the dissolution rate on the surface charge of anodic oxide film. Annealing of porous alumina films for 1 h at 200 °C leads to disappearance of layers with different dissolution rates in the barrier oxide. We explained this phenomenon by the absence of the space charge in the barrier oxide of such films.     

Ultrasound-assisted extraction of capsaicinoids from Capsicum frutescens on a lab- and pilot-plant scale

The influence of operating parameters (solvent type, powder to solvent ratio and temperature) on the ultrasonically assisted extraction of capsaicinoids from dried Capsicum frutescens (fruit) was studied. From the economic perspective, the suitable condition for capsaicinoid extraction by indirect sonication in an ultrasonic bath with a working frequency of 35 kHz was at a ratio of 1g of solid material: 5 ml of 95% (v/v) ethanol, 45 degrees C, where 85% of the capsaicinoids were removed from the raw material in 3h. In an experimental pilot study in 20-l extraction tank at the fixed ultrasonic frequency of 26 kHz and 70 kHz, the recovery of capsaicinoids was 76% and 70%, respectively. It was shown that the ultrasonic extraction produced a significant reduction in extraction time at a lower operational temperature than under a conventional industrial hot maceration process.     

Numerical Simulation of Phase Separation Kinetic of Polymer Solutions Using the Spectral Discrete Cosine Transform Method

A spectral discrete cosine transform (DCT) method was used to solve numerically the spatio-temporal nonlinear Cahn-Hilliard equation for a temperature-induced phase separation process of a polymer solution. The properties of a high molecular weight polystyrene solution were used in the model to reflect the behavior of a real world polymer system. Based on the value of the initial concentration, three different final morphologies of the phase separated system, granular, interconnected, and microcellular, were identified. It was shown that the initial concentration is the main factor to determine the high rate of the phase separation when the phase separation time is the primary desired parameter. The degree of phase separation, as a quantitative measure of the phase separation process, indicates the rate and amount of separated polymer material for practical applications. The model is capable of providing quantitative information of morphology evolution during phase separation processes for microstructure control purposes. The structure factor profile was extracted as a theoretical output that enables comparison with scattering experiments observations as the finger-print of phase separation morphological evolution. It is shown that the DCT method is a very suitable and feasible method for solution of the nonlinear partial differential equation of phase separation kinetics.     

MR imaging of flow with locally high spatial resolution.

Locally focused magnetic resonance imaging (LF MRI) allows imaging with variable spatial resolution within the field of view (FOV). Because LF MRI uses a priori information to provide locally high resolution in regions with rapid spatial variations in intensity (e.g., blood/tissue interface), it allows accurate reproduction of intense sharp edges in the specimen without blurring and truncation artifacts. This study employs LF MRI for 3D imaging of stationary and pulsatile flow. In the implemented version of LF MRI analytically defined basis functions are used to determine image intensity in regions depicted with low or high resolution. It is demonstrated that LF MRI of flow allows a significant (i.e. 3-4 times) reduction in scan time as compared to conventional FT MRI. It is also shown that LF images of pulsatile flow have a decreased appearance of ghosting artifacts as compared to the images reconstructed by using the conventional method.     

Preparation and growth mechanism of micro spherical ammonium dinitramide crystal based on ultrasound-assisted solvent-antisolvent method

Micro-sized spherical ammonium dinitramide (ADN) crystals are successfully prepared by a facile ultrasound-assisted solvent-antisolvent recrystallization method without introducing any additives. The influences of the volume ratio of solvent to antisolvent, the antisolvent temperature and the ultrasound power on the micro-morphologies and properties of ADN crystals are studied systematically. The changes of morphology, particle size, crystal structure and melting point of the ADN crystals are characterized through scanning electron microscopy (SEM), laser particle size analyzer (LPSA), X-ray diffraction (XRD) and differential scanning calorimetry (DSC), respectively. The results show that the optimal experimental parameters for the ADN crystal of spherical morphology are as follows: the volume ratio of solvent to antisolvent is 1:50, the antisolvent temperature is 20 ℃, and the ultrasound power is 70 W. The predicted hexagonal-flake and spherical morphologies for the ADN are close to the experimental morphologies. The growth mechanism of the spherical ADN crystal changes with supersaturation of the ADN solution. As the degree of supersaturation increases, the growth models of the spherical ADN change from the spiral growth to the rough growth, and the morphologies of ADN change from the large-sized ADN ball to the small-sized ADN ball.     

居中热库蛙跳算法的大尺度模拟测试

分子动力学模拟一个必不可少的要素是对运动方程的准确高效积分. 尽管在动力学传播框架内的现代计算工具中大量使用了传统的蛙跳算法,研究表明蛙跳算法仍然可以进一步改进以获得更好的性能. 居中控温方案中蛙跳的改进版本(蛙跳-middle)实现了更高的精度和效率,即使积分时间步长扩大了几倍,也能保持稳定的动力学传播. 本文使用常规和增强采样模拟中对两个积分算法(蛙跳和蛙跳-middle)进行大尺度模拟测试,旨在标定由时间步长引起的全局性质(例如,详细的势能项)的变化行为以及复杂系统的实际模拟中的局部可观察量(例如,自由能变化或键长). 测试集由六个化学和生物相关系统组成,包括$N$-甲基乙酰胺和A₇-T₇DNA中二面角翻转的构象变化、丙二醛内的分子内质子转移、苯和苯酚针对T4溶菌酶L99A的结合自由能计算、乙胺醇低共熔溶剂中的羟基键长变化以及蓝光受体蛋白的势能计算. 所有结果显示蛙跳-middle积分算法中时间步长引起的误差较小. 蛙跳-middle相对传统蛙跳积分算法的性能提高对于全局属性比局部可观测量更大. 总体而言,目前的工作结果表明,在实际化学和生物系统的模拟中,应优先应用蛙跳-middle算法以获得准确的热力学行为和性质.